Cardiac dose and survival in stereotactic lung radiotherapy: results of multi-centre SSBROC trial

Abstract

PURPOSE OR OBJECTIVE: Cardiac toxicity is a potential side effect of thoracic radiotherapy. The majority of studies have been in breast or conventionally fractionated lung radiotherapy patients. While stereotactic ablative body radiotherapy (SABR) is increasingly used in recent years for early stage lung cancer, the impact of dose to the heart, particularly cardiac substructures, in this cohort of patients remains largely unknown. The study looks at doses received by cardiac substructures in SABR patients and impact on survival. MATERIALS AND METHODS: SSBROC 002 is an Australian multi-centre phase II prospective study of SABR for stage I non-small cell lung cancer (ACTRN12614000478617). Patient were treated between 2013-2019 across 9 centres. A previously developed open-source cardiac substructure automatic segmentation tool for delineating 18 cardiac structures (whole heart, 4 chambers, 3 great vessel bases, 4 coronary arteries, 4 cardiac valves and 2 conduction system nodes) was deployed on the planning CTs of patients in this trial. Raw doses to the cardiac structures including mean dose (Dmean), D0-100%, and EQD2 converted doses (voxel-by-voxel conversion using alpha/beta=3) were calculated. Kaplan-Meier analysis of cardiac doses and survival was performed. RESULTS: 118 SABR patients had cardiac substructure doses and survival analysed. 33 patients received 45-50Gy in 5 fractions, 84 received 48Gy in 4 fractions and 1 had 54Gy in 3 fractions. The Dmean of cardiac structures are illustrated in Figure 1. The median of Dmean across all cardiac structures were 0.21 - 0.65Gy for 5 fractions, 0.12 - 0.52Gy for 4 fractions, and 0.07 - 0.20Gy for 3 fractions. However in cases where tumours were close to the heart, Dmean was as high as 22.5Gy to base of superior vena cava and 18.3Gy to sinoatrial node. When converted to EQD2 doses, Dmean reached 34.4Gy and 25.5Gy for these two structures respectively. Similarly for maximum dose (D0), the median D0 across all cardiac structures ranged from 0.3 - 6.3Gy for 5 fractions, 0.2 - 1.6Gy for 4 fractions, 0.1 - 0.3Gy for 3 fractions. However in selected cases D0 was as high as 51.7Gy to the heart and 45.3Gy to the right atrium. This converted to EQD2 of 137.8Gy and 109.5Gy to these two structures. Median follow-up was 35.4 months. For cardiac specific toxicity, 4 patients developed pericardial effusion - 3 cases were grade 2, and 1 grade 3. For overall survival, risk was stratified based on the EQD2 cardiac dose. On univariate analysis, the 50% of cohort who received more than median mean heart dose (MHD) had poorer survival (p=0.00009, Figure 2) compared to the 50% who received below median MHD. Conclusion SABR patients can receive high doses to cardiac substructures. Further multivariate analysis is being performed to assess impact on survival.